Ammonium Chloride → 9-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid amide

Participants

Role	Name	HCID	Charge
Reactant	Ammonium Chloride	HCID 25517	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Sodium Bicarbonate	HCID 516892	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	2-Chloro-6,7-dihydrothieno[2',3':4,5]oxepino[3,2-b]pyridine-9-carboxylic acid	HCID 58203775	—
Solvent	Dimethylformamide	HCID 6228	—
Product	9-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid amide	HCID 58203949	94%

Reaction Steps

A mixture of 9-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid (24.6 g, 87.5 mmol), N,N-Diisopropylethylamine (68 g, 525 mmol), ammonium chloride (18.7 g, 350 mmol) and HATU (66.5 g, 175 mmol) in N,N-Dimethyl-formamide (200 mL) was stirred at r.t. for overnight. The reaction mixture was added saturated sodium bicarbonate. After filtered, the filtrate was concentrated to 23 g of 9-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid amide (yield: 94%)1H-NMR (DMSO, 400 MHz): δ7.96 (d, J=18.4 Hz, 1H), 7.56 (s, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.43 (s, 1H), 7.31 (d, J=4.8 Hz, 1H), 4.33 (t, J=4.8 Hz, 2H), 3.19 (t, J=4.8 Hz, 2H). LC-MS (ESI): m/z=281 [M+H]+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09175009B2
Source dataset	uspto-grants-2015_11
ORD ID	ord-b953de40777f4e92954343b72f69756d
Source note	uspto-grants-2015_11